Varicella-Zoster virus (VZV) causes chickenpox and shingles. After local infection, the virus disseminates through the body in lymphocytes to infect other tissues. The goals of this project are to construct VZV mutants to identify viral genes that are important in virus growth and latency, and to test whether these mutants could serve as candidate live virus vaccines by inoculating animals with the mutants.While the Oka vaccine strain of VZV is able to grow in human lymphocytes and skin in the SCID-hu mouse, an Oka vaccine mutant that was unable to express the VZV ORF47 gene was no longer able to grow in these human tissues. We have also found that the VZV ORF47 protein is required for the full processing (phosphorylation) of the VZV ORF32 protein. In contrast, ORF66 was dispensable for growth in human skin, but contributed to the growth of the virus in lymphocytes. We have also found that VZV genes ORF57 and ORF59 (which encodes uracil DNA glycosylase) are not required for growth of VZV in cell culture. - Chicken pox, shingles, zoster, varicella